{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/34491"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/34491","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"First-order statistical speckle models improve robustness and reproducibility of contrast-enhanced ultrasound perfusion estimates","abstract":"Contrast-enhanced ultrasound (CEUS) permits the quantification and monitoring of adaptive tumor responses in the face of anti-angiogenic treatment, with the goal of informing targeted therapy. However, conventional CEUS image analysis relies on mean signal intensity as an estimate of tracer concentration in indicator-dilution modeling. This discounts additional information that may be available from the first-order speckle statistics in a CEUS image. Heterogeneous vascular networks, typical of tumor-induced angiogenesis, lead to heterogeneous contrast enhancement of the imaged tumor cross-section. To address this, a linear (B-mode) processing approach was developed to quantify the change in the first-order speckle statistics of B-mode cine loops due to the incursion of microbubbles. The technique, named the EDoF (effective degrees of freedom) method, was developed on tumor bearing mice (MDA-MB-231LN mammary fat pad inoculation) and evaluated using nonlinear (two-pulse amplitude modulated) contrast microbubble-specific images. To improve the potential clinical applicability of the technique, a second-generation compound probability density function for the statistics of two-pulse amplitude modulated contrast-enhanced ultrasound images was developed. The compound technique was tested in an antiangiogenic drug trial (bevacizumab) on tumor bearing mice (MDA-MB-231LN), and evaluated with gold-standard histology and contrast-enhanced X-ray computed tomography. The compound statistical model could more accurately discriminate anti-VEGF treated tumors from untreated tumors than conventional CEUS image. The technique was then applied to a rapid patient-derived xenograft (PDX) model of renal cell carcinoma (RCC) in the chorioallantoic membrane (CAM) of chicken embryos. The ultimate goal of the PDX model is to screen RCC patients for de novo sunitinib resistance. The analysis of the first-order speckle statistics of contrast-enhanced ultrasound cine loops provides more robust and reproducible estimates of tumor blood perfusion than conventional image analysis. Theoretically this form of analysis could quantify perfusion heterogeneity and provide estimates of vascular fractal dimension, but further work is required to determine what physiological features influence these measures. Treatment sensitivity matrices, which combine vascular measures from CEUS and power Doppler, may be suitable for screening of de novo sunitinib resistance in patients diagnosed with renal cell carcinoma. Further studies are required to assess whether this protocol can be predictive of patient outcome.","abstract_html":"Contrast-enhanced ultrasound (CEUS) permits the quantification and monitoring of adaptive tumor responses in the face of anti-angiogenic treatment, with the goal of informing targeted therapy. However, conventional CEUS image analysis relies on mean signal intensity as an estimate of tracer concentration in indicator-dilution modeling. This discounts additional information that may be available from the first-order speckle statistics in a CEUS image. Heterogeneous vascular networks, typical of tumor-induced angiogenesis, lead to heterogeneous contrast enhancement of the imaged tumor cross-section. To address this, a linear (B-mode) processing approach was developed to quantify the change in the first-order speckle statistics of B-mode cine loops due to the incursion of microbubbles. The technique, named the EDoF (effective degrees of freedom) method, was developed on tumor bearing mice (MDA-MB-231LN mammary fat pad inoculation) and evaluated using nonlinear (two-pulse amplitude modulated) contrast microbubble-specific images. To improve the potential clinical applicability of the technique, a second-generation compound probability density function for the statistics of two-pulse amplitude modulated contrast-enhanced ultrasound images was developed. The compound technique was tested in an antiangiogenic drug trial (bevacizumab) on tumor bearing mice (MDA-MB-231LN), and evaluated with gold-standard histology and contrast-enhanced X-ray computed tomography. The compound statistical model could more accurately discriminate anti-VEGF treated tumors from untreated tumors than conventional CEUS image. The technique was then applied to a rapid patient-derived xenograft (PDX) model of renal cell carcinoma (RCC) in the chorioallantoic membrane (CAM) of chicken embryos. The ultimate goal of the PDX model is to screen RCC patients for de novo sunitinib resistance. The analysis of the first-order speckle statistics of contrast-enhanced ultrasound cine loops provides more robust and reproducible estimates of tumor blood perfusion than conventional image analysis. Theoretically this form of analysis could quantify perfusion heterogeneity and provide estimates of vascular fractal dimension, but further work is required to determine what physiological features influence these measures. Treatment sensitivity matrices, which combine vascular measures from CEUS and power Doppler, may be suitable for screening of de novo sunitinib resistance in patients diagnosed with renal cell carcinoma. Further studies are required to assess whether this protocol can be predictive of patient outcome.","abstract_has_math":false,"creators":["Lowerison, Matthew R"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Medical Biophysics","degree_department":null,"school":null,"contributors":[],"advisors":["James C. Lacefield","Ann F. Chambers"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-02-09","date_published":"2017-02-09","updated_at":"2026-07-27T21:56:11Z","subjects":["contrast-enhanced ultrasound","speckle statistics","tumor heterogeneity","breast cancer","renal cell carcinoma","anti-angiogenesis"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/34491","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["James C. Lacefield","Ann F. 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In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Contrast-enhanced ultrasound (CEUS) permits the quantification and monitoring of adaptive tumor responses in the face of anti-angiogenic treatment, with the goal of informing targeted therapy. However, conventional CEUS image analysis relies on mean signal intensity as an estimate of tracer concentration in indicator-dilution modeling. This discounts additional information that may be available from the first-order speckle statistics in a CEUS image. Heterogeneous vascular networks, typical of tumor-induced angiogenesis, lead to heterogeneous contrast enhancement of the imaged tumor cross-section. To address this, a linear (B-mode) processing approach was developed to quantify the change in the first-order speckle statistics of B-mode cine loops due to the incursion of microbubbles. The technique, named the EDoF (effective degrees of freedom) method, was developed on tumor bearing mice (MDA-MB-231LN mammary fat pad inoculation) and evaluated using nonlinear (two-pulse amplitude modulated) contrast microbubble-specific images. To improve the potential clinical applicability of the technique, a second-generation compound probability density function for the statistics of two-pulse amplitude modulated contrast-enhanced ultrasound images was developed. The compound technique was tested in an antiangiogenic drug trial (bevacizumab) on tumor bearing mice (MDA-MB-231LN), and evaluated with gold-standard histology and contrast-enhanced X-ray computed tomography. The compound statistical model could more accurately discriminate anti-VEGF treated tumors from untreated tumors than conventional CEUS image. The technique was then applied to a rapid patient-derived xenograft (PDX) model of renal cell carcinoma (RCC) in the chorioallantoic membrane (CAM) of chicken embryos. The ultimate goal of the PDX model is to screen RCC patients for de novo sunitinib resistance. The analysis of the first-order speckle statistics of contrast-enhanced ultrasound cine loops provides more robust and reproducible estimates of tumor blood perfusion than conventional image analysis. Theoretically this form of analysis could quantify perfusion heterogeneity and provide estimates of vascular fractal dimension, but further work is required to determine what physiological features influence these measures. Treatment sensitivity matrices, which combine vascular measures from CEUS and power Doppler, may be suitable for screening of de novo sunitinib resistance in patients diagnosed with renal cell carcinoma. Further studies are required to assess whether this protocol can be predictive of patient outcome."]},{"key":"dc:title","label":"Title","values":["First-order statistical speckle models improve robustness and reproducibility of contrast-enhanced ultrasound perfusion estimates"]}]}],"canonical_facts":{"dc:contributor.advisor":["James C. Lacefield","Ann F. Chambers"],"dc:creator":["Lowerison, Matthew R"],"dc:date.accessioned":["2025-07-10T20:04:29Z"],"dc:date.available":["2025-07-10T20:04:29Z"],"dc:date.issued":["2017-02-09"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). 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To address this, a linear (B-mode) processing approach was developed to quantify the change in the first-order speckle statistics of B-mode cine loops due to the incursion of microbubbles. The technique, named the EDoF (effective degrees of freedom) method, was developed on tumor bearing mice (MDA-MB-231LN mammary fat pad inoculation) and evaluated using nonlinear (two-pulse amplitude modulated) contrast microbubble-specific images. To improve the potential clinical applicability of the technique, a second-generation compound probability density function for the statistics of two-pulse amplitude modulated contrast-enhanced ultrasound images was developed. The compound technique was tested in an antiangiogenic drug trial (bevacizumab) on tumor bearing mice (MDA-MB-231LN), and evaluated with gold-standard histology and contrast-enhanced X-ray computed tomography. The compound statistical model could more accurately discriminate anti-VEGF treated tumors from untreated tumors than conventional CEUS image. The technique was then applied to a rapid patient-derived xenograft (PDX) model of renal cell carcinoma (RCC) in the chorioallantoic membrane (CAM) of chicken embryos. The ultimate goal of the PDX model is to screen RCC patients for de novo sunitinib resistance. The analysis of the first-order speckle statistics of contrast-enhanced ultrasound cine loops provides more robust and reproducible estimates of tumor blood perfusion than conventional image analysis. Theoretically this form of analysis could quantify perfusion heterogeneity and provide estimates of vascular fractal dimension, but further work is required to determine what physiological features influence these measures. Treatment sensitivity matrices, which combine vascular measures from CEUS and power Doppler, may be suitable for screening of de novo sunitinib resistance in patients diagnosed with renal cell carcinoma. Further studies are required to assess whether this protocol can be predictive of patient outcome."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/34491"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["contrast-enhanced ultrasound","speckle statistics","tumor heterogeneity","breast cancer","renal cell carcinoma","anti-angiogenesis"],"dc:title":["First-order statistical speckle models improve robustness and reproducibility of contrast-enhanced ultrasound perfusion estimates"],"dc:type":["thesis"],"thesis:degree_discipline":["Medical Biophysics"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:56:11Z"}